Human Cell-Based Screening Platform Development

NCATS focuses on creating human cell-based models of opioid misuse and addiction and of pain. Through the following three initiatives, NCATS-supported researchers will develop models at the cell, tissue and integrated systems levels. The goal is to develop accurate research models that reflect the complexity of human biology and better predict how potential new drugs will affect humans.

NCATS-led Preclinical NIH HEAL Initiative. Human Cell-Based Screening Platforms and Novel Drugs to Treat Pain, Addiction, and Overdose. A diagram showing NCATS’s plans to make human cell-based platforms available as models to test new treatments for pain, addiction, and overdose. Labeled “Human Cell-Based Platforms for testing new treatments,” the diagram shows a range of model complexity from cells to multi-organ models, illustrating that these platforms will enable researchers to test and study potential drugs in human cells, tissues, and organs, before they are administered to humans in clinical trials. It begins with a microscopic image of neurons derived from induced pluripotent stem cells, followed by a microscopic image of 3-D bioprinted tissues, and finally followed by an image of tissue chips, which are tissues that have been developed and organized to represent functioning and connected organs.

iPSC-Derived Neurons for Pain, Addiction and Overdose

Scientists in NCATS’ Stem Cell Translation Laboratory (SCTL) are developing a renewable supply of human cell-based models, focusing on patient-derived induced pluripotent stem cell (iPSC) lines that give rise to specialized, functional nerve cells that are relevant for opioid misuse and addiction and for pain. NCATS offers robotic manufacturing of validated and quality-controlled human cells with the intent of making subsequent tests reproducible and reliable. These cells can be used in models to leverage diverse research projects that the Center conducts or supports. Through its Division of Preclinical Innovation, NCATS will provide access to iPSC lines, iPSC-derived cell types, protocols, cutting-edge technologies and multidisciplinary scientific expertise.

3-D Bioprinted Tissue Models of Pain, Opioid Use Disorder and Overdose for Drug Screening

NCATS’ 3-D Tissue Bioprinting program experts will develop complex human, biologically relevant, 3-D tissue-in-a-well models of addiction, pain and the blood-brain barrier for high-throughput drug screening, using bioprinting techniques, iPSC-derived neurons and other cells supplied by the SCTL. Collaborators will have access to NCATS’ research resources.

NCATS also supports collaborations with the external research community to develop and use 3-D biofabricated tissue models as novel drug screening platforms to advance preclinical discovery and development of non-addictive treatments for pain, opioid use disorder and overdose. Projects have two phases. During the initial phase, scientists will apply 3-D biofabrication technologies to develop novel multicellular tissue systems for drug screening, using human iPSC-derived cells representing sensory/pain neurons, brain regions, and other tissues involved in pain, addiction and overdose, including tissue models of the blood-brain barrier. In the second phase, researchers will test the new systems for drug screening. View RFA-TR-19-005 to learn more.

Tissue Chips to Model Pain, Addiction and Overdose

NCATS provides funding for investigators to create and test devices that can model the mechanisms or effects of pain-relevant signaling, addiction, or opioid use disorders, using human tissues in in vitro tissue- and organ-on-chip systems. Tissue chip systems are promising platforms because they can closely mimic human physiology and can model normal and diseased states. View RFA-TR-19-003 to learn more.